Two-Component Signal Transduction Systems in the Human Pathogen Streptococcus agalactiae

Abstract

Streptococcus agalactiae (group B Streptococcus [GBS]) is an important cause of invasive infection in newborns, maternal women, and older individuals with underlying chronic illnesses. GBS has many mechanisms to adapt and survive in its host, and these mechanisms are often controlled via two-component signal transduction systems. In GBS, more than 20 distinct two-component systems (TCSs) have been classified to date, consisting of canonical TCSs as well as orphan and atypical sensors and regulators. These signal transducing systems are necessary for metabolic regulation, resistance to antibiotics and antimicrobials, pathogenesis, and adhesion to the mucosal surfaces to colonize the host. This minireview discusses the structures of these TCSs in GBS as well as how selected systems regulate essential cellular processes such as survival and colonization. GBS contains almost double the number of TCSs compared to the closely related Streptococcus pyogenes and Streptococcus pneumoniae, and while research on GBS TCSs has been increasing in recent years, no comprehensive reviews of these TCSs exist, making this review especially relevant.

Keywords: group B Streptococcus; signal transduction; two-component system.

FIG 1

Structure and domain architecture of GBS TCS histidine kinases. (Left) Schematic of intramembrane histidine kinases (IM-HK) and individual sensor kinase domains of predicted IM-HKs in GBS. (Right) Schematic of extracellular histidine kinases and sensor kinase domains of predicted GBS extracellular sensors. Domains predicted using Pfam (https://pfam.xfam.org/) and SMART (http://smart.embl-heidelberg.de/). Predicted transmembrane domains are shown in blue, HAMP domains are represented by green squares, histidine kinase domains are red diamonds, and H-ATPase domains are gray hexagons. Pink lightning bolts signify the likely site of signal sensing. Domain architecture is not fully to scale. (Adapted from mBio [22].)

FIG 2

Model of regulation by selected GBS two-component systems. Selected GBS TCSs are shown along with genes they have been demonstrated to regulate. TCSs are separated into three sections based on predicted primary cellular functions: colonization in blue, pathogenesis in purple, or cell wall modifications and resistance to cationic antimicrobial peptides in green.